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Updated: Jun 6, 2026
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Monitoring ER/SR Calcium Release with the Targeted Ca2+ Sensor CatchER+
Published on: May 19, 2017
Complexin clamps asynchronous release by blocking a secondary Ca(2+) sensor via its accessory α helix
Xiaofei Yang1, Yea Jin Kaeser-Woo, Zhiping P Pang
1Department of Molecular and Cellular Physiology, Stanford University, 1050 Arastradero Road, Palo Alto, CA 94304-5543, USA.
Neuron
|December 15, 2010
Summary
Complexin has dual roles in neurotransmitter release, activating synchronous release by priming vesicles and clamping spontaneous release by blocking a secondary Ca(2+) sensor. Its functions are crucial for regulating synaptic vesicle exocytosis.
Area of Science:
- Neuroscience
- Molecular Biology
- Cell Biology
Background:
- Neurotransmitter release is a tightly regulated process involving synaptic vesicle exocytosis.
- Complexin and synaptotagmin-1 are key proteins involved in regulating this release.
- Complexin's roles in activating and clamping exocytosis are distinct from synaptotagmin-1.
Purpose of the Study:
- To elucidate the distinct activation and clamping mechanisms of complexin in neurotransmitter release.
- To investigate how complexin interacts with the SNARE complex and Ca(2+) sensors.
- To understand the role of complexin's specific domains in regulating synaptic vesicle exocytosis.
Main Methods:
- Site-directed mutagenesis of complexin and synaptobrevin-2.
- Analysis of synaptic vesicle exocytosis (synchronous, spontaneous, and asynchronous).
- Investigating the interaction of complexin with SNARE complexes and Ca(2+) sensors.
Main Results:
- Complexin activates synchronous exocytosis by promoting vesicle priming.
- Complexin clamps spontaneous and asynchronous exocytosis by blocking a secondary Ca(2+) sensor.
- Complexin's N-terminal region and accessory α helix mediate distinct activation and clamping functions, respectively.
- The accessory α helix likely inserts into SNARE complexes to block assembly until Ca(2+) binding to synaptotagmin relieves the block.
- A mutation in synaptobrevin-2 also unclamps spontaneous fusion, suggesting a role in force transfer.
Conclusions:
- Complexin possesses distinct activation and clamping functions essential for precise neurotransmitter release.
- Complexin's accessory α helix acts as a clamp by interfering with SNARE complex assembly.
- Complexin collaborates with synaptotagmin-1 to control trans-SNARE complex formation and regulate exocytosis.
- These findings provide a deeper mechanistic understanding of synaptic transmission regulation.
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